Impact of adverse events on costs and quality of life in protease inhibitor-based combination therapy for hepatitis C.
Protease inhibitor with pegylated interferon and ribavirin therapy (PI-PR) increases hepatitis C virus treatment efficacy versus standard of care pegylated interferon and ribavarin therapy [PR]. The adverse event (AE) impact of PI-PR remains under-reported. The authors estimated the AE impact on costs, treatment discontinuation and health-related quality of life (HRQoL) in PI-PR- and PR-treated patients through literature review and cost analysis. HRQoL and safety data were synthesized by instrument, AE and discontinuation rate. AE-related treatment costs were estimated with trial-based AE rates and literature-based protocols, resource utilization and standard costs. No PI-PR study reported HRQoL outcomes. Five PR studies reported that anemia, depression, fatigue and/or influenza-like symptoms negatively affected HRQoL. Decreased HRQoL predicted treatment discontinuation in two PR studies. PI-PR and PR had comparable AE-related treatment discontinuation rates (~12%). Weighted AE-related treatment costs were US$2042, $1835 and $1076 in boceprevir-based PI-PR, PR and telaprevir-based PI-PR, respectively. AE-related burden may increase with PI-PR. Future studies should incorporate AE-related economic and HRQoL outcomes to comprehensively assess costs/benefits.


[Terminal ballistics. 3].
This brief chapter, focusing essentially on a single topic, has been written in homage to Emile Theodor Kocker, a masterful exponent of the art of surgery and founder of the culture of terminal ballistics. For most of the literature we are indebted to Fackler and Dougherty, who, with the particular grasp, and fair of historians, act as guides on a trial which is only apparently retrograde, but which actually bears eloquent witness to the fact that even in the most physically tangible of arts, namely the art of surgery, inspired curiosity may help us to go well beyond the limits of our day and age. This chapter is also dedicated to the memory of another great surgeon, Vittorio Pettinari, who for one of the authors was an incomparable mentor and past-master of such curiosity.


A qualitative study of risk and resilience in young adult women with a history of juvenile-onset fibromyalgia.
Juvenile-onset Fibromyalgia (JFM) is a chronic pain condition characterized by widespread musculoskeletal pain, fatigue, sleep difficulties, mood concerns, and other associated symptoms. Although diagnosed in childhood, JFM often persists into adulthood can result in continued physical, social, and psychological impairment. The purpose of this qualitative study was to identify themes of risk and resilience for long-term outcomes among young adults diagnosed with JFM in childhood. The sample included 13 young adults (ages 26-34) who had been diagnosed with JFM in adolescence. Focus groups were used to elicit qualitative information about living with JFM and perceived challenges and buffering factors impacting their adjustment. The majority of participants (80%, N = 12) continued to meet criteria for fibromyalgia (FM). An iterative, thematic analysis revealed themes of resilience (e.g., greater acceptance, re-setting expectations, active coping, addressing mental health) and risk (e.g., lack of information, stigma, isolation, negative healthcare experiences). Results suggest the need for longer follow-up of youth with JFM as they transition to adulthood with multidisciplinary care and more attention to education about JFM and associated symptoms such as fatigue, as well as ongoing support for coping and mental health needs. A holistic approach to care during the transition years could be beneficial to minimize impact of JFM on long-term functioning.


Determining the Optimal Outcome Measures for Studying the Social Determinants of Health.
Americans have significantly poorer health outcomes and shorter longevity than citizens of other industrialized nations. Poverty is a major driver of these poor health outcomes in the United States. Innovative anti-poverty policies may help reduce economic malaise thereby increasing the health and longevity of the most vulnerable Americans. However, there is no consensus framework for studying the health impacts of anti-poverty social policies. In this paper, we describe a case study in which leading global experts systematically: (1) developed a conceptual model that outlines the potential pathways through which a social policy influences health, (2) fits outcome measures to this conceptual model, and (3) estimates an optimal time frame for collection of the selected outcome measures. This systematic process, called the Delphi method, has the potential to produce estimates more quickly and with less bias than might be achieved through expert panel discussions alone. Our case study is a multi-component randomized-controlled trial (RCT) of a workforce policy called MyGoals for Healthy Aging.


[Treatment of large mandibular cysts (author's transl)].
Apart from certain particular types of lesions, the diagnosis of a histologically benign "large mandibular cyst" (paradental cyst, epidermal cyst, ameloblastoma...) should lead to an attempt at conservative treatment: this does not alter mandibular continuity and if possible, the inferior dental neurovascular pedicle, the soft tissues of the buccal lining, and the dental organs. It is finally the gross pathological findings and if necessary the results of an extemporaneous histological examination that will supply the information leading to the choice of the best type of treatment: marsupialization, enucleation, curettage, "pressure curettage", uninterrupting resection. This attitude requires prolonged postoperative radiological supervision and does not exclude the need for an interrupting resection in unfavourable cases at a later date.


[Antioxidant parameters in metabolic syndrome -- a dynamic evaluation during oral glucose tolerance test].
Patients with metabolic syndrome show augmented cardio-vascular risk, at least in part mediated through disequilibrium between mechanisms generating free radicals, and antioxidant defense. Carbohydrate and lipid disturbances in metabolic syndrome induce oxidative stress via several non fully understood mechanisms. Glucose overload in oral glucose tolerance test (OGTT) can also induce oxidative stress. The aim of our study was to evaluate changes in superoxide dismutase and glutathione peroxidase activity, as well as total antioxidant status in OGTT in patients with metabolic syndrome and in healthy subjects. OGTT was performed in 36 healthy volunteers and in patients with metabolic syndrome. Glucose, Insulin, and triglycerides were evaluated at 0th, 30th, 60th, 120th, and 180th min. Superoxide dismutase and glutathione peroxidase were measured at 0th, 60th, and 120th min. Total antioxidant status was measured at 0th, and 120th min. At 0th min total, HDL and LDL cholesterol were evaluated. A statistically significant decrease (p < 0.05) in superoxide dismutase activity at 120th as compared with 60th min were observed. Glutathione peroxidase activity decreased significantly (p < 0.05) even though at 60th as compared with 0th min and remained decreased at 120th min. Total antioxidant status was found to be increased (p < 0.05) at 120th as compared with 0th min. The observed dynamic in patients did not differed (p > 0.05) from control group. The study shows a decrease in antioxidant enzyme activity and a compensatory increase in total antioxidant status, indicating a surcharge of antioxidant homeostasis. In context of carbohydrate and lipid disturbances in metabolic syndrome, this is to suggest an existing of complementary pathogenic mechanisms, able to aggravate cardiovascular risk in these patients. Correction of metabolic disturbances may be an efficacious tool for influencing on prooxidant-antioxidant homeostasis too.


Characterization of Glutathione Dithiophosphates as Long-Acting H2S Donors.
Considering the important cytoprotective and signaling roles but relatively narrow therapeutic index of hydrogen sulfide (H2S), advanced H2S donors are required to achieve a therapeutic effect. In this study, we proposed glutathione dithiophosphates as new combination donors of H2S and glutathione. The kinetics of H2S formation in dithiophosphate solutions suggested a continuous H2S release by the donors, which was higher for the dithiophosphate of reduced glutathione than oxidized glutathione. The compounds, unlike NaHS, inhibited the proliferation of C2C12 myoblasts at submillimolar concentrations due to an efficient increase in intracellular H2S. The H2S donors more profoundly affected reactive oxygen species and reduced glutathione levels in C2C12 myocytes, in which these parameters were elevated compared to myoblasts. Oxidized glutathione dithiophosphate as well as control donors exerted antioxidant action toward myocytes, whereas the effect of reduced glutathione dithiophosphate at (sub-)micromolar concentrations was rather modulating. This dithiophosphate showed an enhanced negative inotropic effect mediated by H2S upon contraction of the atrial myocardium, furthermore, its activity was prolonged and reluctant for washing. These findings identify glutathione dithiophosphates as redox-modulating H2S donors with long-acting profile, which are of interest for further pharmacological investigation.


Arachidonic acid acts as an intracellular activator of NADPH-oxidase in Fc gamma receptor-mediated superoxide generation in macrophages.
A protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), inhibited phorbol ester (12-o-tetradecanoylphorbol 13-acetate)-induced and Fc gamma receptor-mediated superoxide anion (O2-) generations in guinea pig macrophages, but the inhibitory effect on Fc gamma receptor-mediated O2- generation was only partial. Both O2- generations were inhibited extensively by a phospholipase A2 inhibitor, 4-p-bromophenacyl bromide (4-pBPB). It was confirmed in control experiments that H-7 and 4-pBPB had no direct inhibitory effect on NADPH-oxidase activity. Dose-dependent stimulation of O2- generation was induced by arachidonate in macrophages, and the arachidonate-induced O2- generation was not inhibited by H-7. Arachidonate could also induce NADPH-oxidase activation in a post-nuclear fraction obtained from unstimulated macrophages and this activation was not inhibited by H-7, indicating that protein kinase C activation was not involved in this cellfree system. These results support the hypothesis that the O2- generation induced by Fc gamma receptor stimulation is mainly mediated by arachidonic acid which is released by the action of phospholipase A2 activated by receptor stimulation. Arachidonic acid seems to be acting rather directly in activating the NADPH-oxidase system of macrophage membrane. Protein kinase C may have a significant role in Fc gamma receptor-mediated O2- generation but it is not obligatory, and protein kinase C seems to activate NADPH-oxidase rather indirectly, probably by inducing the arachidonic acid release.


In vivo antitumor activity by 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone in a solid human carcinoma xenograft model.
Previously we have shown that 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), which is isolated from the buds of Cleistocalyx operculatus, significantly inhibits the growth of human liver cancer SMMC-7721 cells and is able to induce apoptosis of SMMC-7721 cells in vitro. Here we report the antitumor effects of DMC in vivo, using a solid human tumor xenograft mouse model using human liver cancer SMMC-7721 cells. The average tumor weights in the control group and in mice injected with 150 mg/kg DMC were 1.42+/-0.11 g and 0.59+/-0.12 g, respectively. Flow cytometric analysis of the tumor cell population demonstrated an aneuploid peak (representing 33.60+/-0.80% of the total in mice injected with 150 mg/kg DMC). To our knowledge, this is the first time that chalcone compounds have been applied to a human tumor xenograft model.


Polymerization of ionized acetylene clusters into covalent bonded ions: evidence for the formation of benzene radical cation.
Since the discovery of acetylene and benzene in protoplanetary nebulae under powerful ultraviolet ionizing radiation, efforts have been made to investigate the polymerization of ionized acetylene. Here we report the efficient formation of benzene ions within gas-phase ionized acetylene clusters (C2H2)n+ with n = 3-60. The results from experiments, which use mass-selected ion mobility techniques, indicate that the (C2H2)3+ ion has unusual stability similar to that of the benzene cation; its primary fragment ions are similar to those reported from the benzene cation, and it has a collision cross section of 47.4 A2 in helium at 300 K, similar to the value of 47.9 A2 reported for the benzene cation. In other words, (C2H2)3+ structurally looks like benzene, it has stability similar to that of benzene, it fragments such as benzene, therefore, it must be benzene!


What's your board's culture?
You have a board culture whether you know it or not. Every board creates a governance culture--a pattern of beliefs, traditions and practices-that prevails at meetings. Some work well; others get in the way.


Societal context and the production of immigrant status-based health inequalities: a comparative study of the United States and Canada.
We compare disparities in health status between first-generation immigrants and others in the United States (US) and Canada. We used data from the Joint Canada-US Survey of Health. The regression models adjusted for demographics, socioeconomic status, and health insurance (the US). In both countries, the health advantage belonged to immigrants. Fewer disparities between immigrants and those native-born were seen in Canada versus the US. Canadians of every immigrant/race group fared better than US native-born Whites. Fewer disparities in Canada and better overall health of all Canadians suggest that societal context may create differences in access to the resources, environments, and experiences that shape health and health behaviors.


Transparent Omniphobic Coating with Glass-Like Wear Resistance and Polymer-Like Bendability.
Transparent omniphobic or anti-smudge coatings with glass-like wear resistance and polymer-like bendability have many potential applications but there are no reports of such materials. We Report herein a molecular composite possessing these properties. The composite is prepared via the photo-initiated ring-opening polymerization of the epoxide rings of glycidyloxypropyl polyhedral silsesquioxane (GPOSS). While the desired hardness is provided by the silica core, the flexibility is imparted by the glycidyloxypropyl network. Oil and water repellency is achieved without adversely affecting the other properties by incorporating a low-surface-tension liquid lubricant poly(dimethyl siloxane). On the final coating, various organic solvents and water readily and cleanly glide, while complex fluids, such as ink and paint facilely contract. These properties are retained after an initially flat coating sample is rolled into a U-shape 500 times or is abraded with steel wool.


Effectiveness of doramectin for treatment of experimentally induced gastrointestinal tract larval nematode infections in calves.
Anthelmintic efficacy of doramectin, a macrocyclic lactone of the avermectin family, was evaluated against larval parasitic nematodes in calves. The investigational product was given SC at a dosage of 0.2 mg/kg of body weight to 10 calves infected 6 days previously with third-stage larvae of the genera Haemonchus, Ostertagia, Cooperia, and Nematodirus. Ten additional calves with identical larval exposure were given saline solution SC also at 6 days after inoculation, and served as the nonmedicated controls. At 14 or 15 days after treatment, the calves were slaughtered in complete replicate for nematode recovery and subsequent quantifications. In comparing nematode numbers at necropsy for the saline- and doramectin-treated groups, nematocidal effectiveness as directed against fourth-stage larvae was: 100% for Haemonchus placei and Cooperia spp, > 99% for Ostertagia ostertagi, and 64.5% for Nematodirus helvetianus. All treatments were easily administered, and adverse behavioral or tissue reactions were not seen to result from doramectin administration.


The effect of supplementary protein on in vivo metabolism of the mammary gland in lactating dairy cows.
Four lactating cows equipped with rumen and duodenal cannulas were fed a diet of grass silage and concentrates containing either 12.4 or 17.2% CP (DM basis) in a change-over design. Additional protein was supplied as white fish meal. Fish meal did not affect molar proportions of VFA in the rumen, but duodenal NAN supply was increased .69 g/g of N in supplementary feed. In Experiment 2, three lactating dairy cows that had been prepared with catheters across the mammary gland were fed the same diets using a switchback design. Blood samples were taken to determine changes in metabolite flux to the mammary gland. In both experiments, milk production and protein yield were nonsignificantly increased by addition of fish meal. Milk urea output was increased from 3.18 to 4.74 g/d by fish meal supplementation, reflecting increased arterial concentrations of urea. Concentrations of glucose, VFA, and BHBA in blood showed no substantial changes because of dietary supplementation of fish meal. Supply of essential AA increased 26% with fish meal supplementation, mammary uptake increased 34%, but milk protein output only increased 5%. The low efficiency of conversion of supplementary protein to milk protein appears to be related to the inability of the gland to utilize the additional AA.


Contribution of peripheral endothelin ETA and ETB receptors in neuropathic pain induced by spinal nerve ligation in rats.
Endothelins (ETs) contribute to the sensory changes seen in animals models of inflammatory, cancer and diabetic neuropathic pain, but little is known about their nociceptive role following peripheral nerve injury. The current study evaluated mechanisms by which ETs can drive changes in nociceptive responses to thermal stimulation of the hind paw of rats induced by unilateral lumbar L5/L6 spinal nerve ligation (SNL) injury. SNL sensitizes rats to acetone-evoked cooling of and radiant heat application (Hargreaves test) to the ipsilateral hind paw (throughout 3-40 and 9-40 days after surgery, respectively). At 12 days after SNL, intraplantar (i.pl.) injection of endothelin-1 (ET-1, 10 pmol) induces greater overt nociception that was reduced only by treatment with the selective ET(A) peptidic antagonist (BQ-123, 10 nmol, i.pl), but unchanged by the selective ET(B) peptidic antagonist (BQ-788). Cold allodynia evoked by cooling the ipsilateral hind paw with acetone was reduced by i.pl. injection of both antagonists BQ-123 or BQ-788 (3 or 10 nmol). In contrast, heat hyperalgesia evaluated by Hargreaves method was reduced only by BQ-123. SNL enhanced the [Ca(+2)](i) increases induced by ET-1 (100 nM) in neurons from L5/L6 (injured) and L4 (intact) cultured dorsal root ganglion, but did not change the responses of non-neuronal cells. Furthermore, Western blot analysis revealed that SNL increased ET(A) and ET(B) receptor protein expression in spinal nerves. Thus, SNL induces marked hind paw hypersensitivity to thermal stimulation in part via up-regulation of peripheral sensory nerve pronociceptive ET(A) and ET(B) receptor-operated mechanisms.


Microalgal lipids production and nutrients recovery from landfill leachate using membrane photobioreactor.
The aim of this work was to realize high-efficiency nutrients recovery from landfill leachate (LL) for microalgal lipids production. Negative effects of LL on microalgal lipid synthesis was revealed and a scalable membrane-based tubular photobioreactor (SM-PBR) was proposed to offset these negative effects. Microalgal biomass concentration was improved from 0 g/L in the traditional PBR to 2.13 g/L in the SM-PBR. Major operating conditions were optimized to enhance nutrients recovery and lipid productivity. The maximum N recovery efficiency of 74.31% and the maximum daily lipid production of 404.98 mg/d were obtained under the volume ratio of 5:3 (microalgae culture/LL stream) and phosphate feeding concentration of 50 mg/L. The obtained lipid was convinced to have a good combustion and anti-degradation property, with high cetane number (>52%) and low linolenic acid content (<12%). The SM-PBR provided a feasible approach for large-scale microalgal lipid production with LL.


Chemical Synthesis and Applications of Colloidal Metal Phosphide Nanocrystals.
Colloidal nanocrystals (NCs) have emerged as promising materials in optoelectronic devices and biological imaging application due to their tailorable properties through size, shape, and composition. Among these NCs, metal phosphide is an important class, in parallel with metal chalcogenide. In this review, we summarize the recent progress regarding the chemical synthesis and applications of colloidal metal phosphide NCs. As the most important metal phosphide NCs, indium phosphide (InP) NCs have been intensively investigated because of their low toxicity, wide and tunable emission range from visible to the near-infrared region. Firstly, we give a brief overview of synthetic strategies to InP NCs, highlighting the benefit of employing zinc precursors as reaction additive and the importance of different phosphorus precursors to improve the quality of the InP NCs, in terms of size distribution, quantum yield, colloidal stability, and non-blinking behavior. Next, we discuss additional synthetic techniques to overcome the issues of lattice mismatch in the synthesis of core/shell metal phosphide NCs, by constructing an intermediate layer between core/shell or designing a shell with gradient composition in a radial direction. We also envision future research directions of InP NCs. The chemical synthesis of other metal phosphide NCs, such as II-V metal phosphide NCs (Cd3P2, Zn3P2) and transition metal phosphides NCs (Cu3P, FeP) is subsequently introduced. We finally discuss the potential applications of colloidal metal phosphide NCs in photovoltaics, light-emitting diodes, and lithium ion battery. An overview of several key applications based on colloidal metal phosphide NCs is provided at the end.


[Clinical results of cefaclor treatment of infections of oral regions].
Cefaclor (CCL) is a cephem antibiotic for oral use. Thirty cases of infection of oral regions, in the First Department of Oral and Maxillofacial Surgery, School of Dentistry, the University of Tokushima, were treated with CCL at 750 mg/day. The results were as follows: The efficacy rate for all kinds of diseases was 80.0% in 3 days and 96.7% in 5 days and 86.7% as an overall assessment by the patients' doctors. With regard to the degree of symptoms, the efficacy rate for cases with moderate symptoms was less than that for mild cases in 3 days and according to the assessment by the patients' doctors. Some moderate cases required increased medication because no beneficial effect was observed. In sensitivity tests, CCL was shown to be effective on all 27 isolated clones of bacteria tested. CCL caused no detectable changes in laboratory data. No side effects were observed in any case. From these results, it is concluded that CCL is a highly effective antibiotic for use on infections of the oral regions.


Automated versus physician assignment of cause of death for verbal autopsies: randomized trial of 9374 deaths in 117 villages in India.
Verbal autopsies with physician assignment of cause of death (COD) are commonly used in settings where medical certification of deaths is uncommon. It remains unanswered if automated algorithms can replace physician assignment. We randomized verbal autopsy interviews for deaths in 117 villages in rural India to either physician or automated COD assignment. Twenty-four trained lay (non-medical) surveyors applied the allocated method using a laptop-based electronic system. Two of 25 physicians were allocated randomly to independently code the deaths in the physician assignment arm. Six algorithms (Naïve Bayes Classifier (NBC), King-Lu, InSilicoVA, InSilicoVA-NT, InterVA-4, and SmartVA) coded each death in the automated arm. The primary outcome was concordance with the COD distribution in the standard physician-assigned arm. Four thousand six hundred fifty-one (4651) deaths were allocated to physician (standard), and 4723 to automated arms. The two arms were nearly identical in demographics and key symptom patterns. The average concordances of automated algorithms with the standard were 62%, 56%, and 59% for adult, child, and neonatal deaths, respectively. Automated algorithms showed inconsistent results, even for causes that are relatively easy to identify such as road traffic injuries. Automated algorithms underestimated the number of cancer and suicide deaths in adults and overestimated other injuries in adults and children. Across all ages, average weighted concordance with the standard was 62% (range 79-45%) with the best to worst ranking automated algorithms being InterVA-4, InSilicoVA-NT, InSilicoVA, SmartVA, NBC, and King-Lu. Individual-level sensitivity for causes of adult deaths in the automated arm was low between the algorithms but high between two independent physicians in the physician arm. While desirable, automated algorithms require further development and rigorous evaluation. Lay reporting of deaths paired with physician COD assignment of verbal autopsies, despite some limitations, remains a practicable method to document the patterns of mortality reliably for unattended deaths. ClinicalTrials.gov , NCT02810366. Submitted on 11 April 2016.


The fragile site WWOX gene and the developing brain.
WWOX was cloned as a tumor suppressor gene mapping to chromosomal fragile site FRA16D. Loss of WWOX is closely related to tumorigenesis, cancer progression, and therapy resistance. Recent studies demonstrate the growing role of WWOX gene in other human pathologies such as metabolic and nervous system-related conditions. The neurologic phenotype of WWOX mutation includes seizures, ataxia, developmental delay, and spasticity of variable severity. WWOX is a ubiquitous protein with high expression in many tissues including brain, cerebellum, brain stem, and spinal cord. WWOX is highly expressed in different brain regions during murine fetal development and remained unchanged in the cortex and the corpus callosum in adult mice. The mechanism or the putative role of WWOX in the nervous system is still unclear but may include abnormal signaling protein, disruption of neuronal pathways, neuronal differentiation, mitochondrial dysfunction, or apoptosis. Homozygous mutations affecting WWOX in humans are likely to be more described in the future using exome sequencing. The described findings highlight that WWOX plays a critical role in normal central nervous system development and disease. The aim of this review is to summarize the roles of WWOX in the developing brain.


Skin nodules associated with parasitism with Henneguya sp. (Cnidaria: Myxosporea) in the neotropical fish Cyphocharax modestus.
A new myxozoan species, Henneguya sp., is described based on material from skin of Cyphocharax modestus. Mature myxospores are were elongate and ellipsoidal, measuring 21.4 ± 1.2 (19.4-23.2) μm in total length, 5.1 ± 0.3 (4.5-5.8) μm in width, 11.9 ± 0.5 (10.9-12.7) μm in body length and 9.6 ± 0.7 (8.4-10.5) μm in length of the caudal process. The polar capsules were elongated and had unequal sizes, with length of 5.1 ± 0.4 (4.5-6.0) μm and 5.6 ± 0.4 (4.9-6.3) μm for smaller and larger respectively and width of 1.8 ± 0.2 (1.4-2.0) μm. The larger polar capsule had 8 turns in polar filament while the smaller polar capsule had 5 turns in polar filament. The macroscopic analysis revealed the presence of large nodules, which were located before and after the dorsal fin of the hosts. The histopathological analysis showed the development of nodules filled with plasmodia, surrounded by loose connective tissue, developed in the dermis of the skin. Many cysts containing countless spores, as well as free spores, were located in the dermis and hypodermis of the hosts, causing the disorganization of the connective tissue that is responsible for the support. This is the first record of a Henneguya species in C. modestus.


Optimization of biomethane production from sweet sorghum bagasse using artificial neural networks combined with particle swarm algorithm.
In the face of international movement away from fossil fuels caused pollution menace, many research labs are rushing towards next big breakthrough via effective biorefinery development employing non-edible agro-residues as feedstock. This work aims to evaluate and optimize the methane potential of underutilized full strength sweet sorghum bagasse (SSB) via anaerobic digestion (AD). Biochemical methane potential assays are set up for SSB AD under mesophilic and thermophilic conditions at four substrate-o-inoculum ratios (SIR) 3, 5, 7, and 9 with pH 6.5, 7.5, and 8.5 and with 80, 90, and 100 rpm mixing speed over 50 days. SIR 5 produced the highest cumulative biomethane yield of 4.25 L methane g-1 VS with a shorter lag time of 7.5 days and technical digestion time of 24 days. The influence of physio-chemical parameters on AD process dynamics is supported with 16s rRNA metagenomic sequencing. Based on complete experimental data sets, two artificial neural network (ANN) models are developed to identify the relevant significance of process parameters and to predict bagasse methane potential. Further, the developed ANN model is integrated with particle swarm optimization algorithm to create ideal AD process operating conditions which maximize the target variable, biomethane. The trained and cross-validated ANN-PSO model showed good-fit-accuracy with R2 > 0.995 and demonstrated satisfactory performance in the biomethane yield prediction from AD of non-edible agri-residues.


MitoKATP regulating HIF/miR210/ISCU signaling axis and formation of a positive feedback loop in chronic hypoxia-induced PAH rat model.
In the present study, we studied the mechanism of mitochondrial ATP-sensitive potassium (mitoKATP) channels regulating hypoxia-inducible factor (HIF)-1α/microRNA (miR)-210/mitochondrial iron-sulfur protein integrin (ISCU) signaling axis and forming a positive feedback loop in chronic hypoxia-induced pulmonary arterial hypertension (PAH) by using in vivo animal model. Two hundred healthy adult SPF Sprague-Dawley rats were randomly divided into five groups: Control, a mimic miR-210 agent (mimic-210) intervention, a miR-210 inhibitor (anti-210) intervention, a chronic PAH and an anti-210 intervention PAH groups, with 40 rats in each group. After the chronic PAH rat model was successfully established, the rats were intervened with mimic-210 and anti-210. The pulmonary artery smooth muscle cells (PASMCs) of rats in each group were acutely isolated and the activity of mitoKATP and mitochondria-derived oxygen free radicals reactive oxygen species (ROS) was detected. RT-qPCR was used to detect the gene of HIF-1α/miR-210/ISCU and western blot analysis was used to detect the protein of HIF-1α and ISCU. The gene and protein expression were detected again after mitoKATP-specific opener diazoxide and blocker 5-HD was given via tail vein and took effect on each group of rats, respectively. Additionally, the indicators were detected again after ISCU recombinant protein was given via tail vein and ISCU small interfering RNA (siRNA) via nasal feeding and took effect on each group of rats, respectively. It was found that the activity of mitoKATP and ROS and the gene and protein levels of HIF-1α/miR-210/ISCU of the mimic-210 group were significantly higher than those of the control group while that of the anti-210 group was significantly reduced (P<0.05). The indicators in the chronic PAH group were significantly higher than those of the control group while those of the anti-210 intervention PAH group were significantly reduced (P<0.05). The indicators of all the groups were increased after being given mitoKATP specific opener diazoxide. The indicators of all the groups were significantly reduced after receiving blocker 5-HD (P<0.05). The indicators of all the groups were significantly reduced after given ISCU recombinant protein. The indicators of all the groups increased following ISCU siRNA, and there was a statistically significant difference (P<0.05). In conclusion, the mechanism of mitoKATP regulating the HIF-1α/miR-210/ISCU signaling axis and formation of a positive feedback loop exists in the PAH rat model.


The production of a macrophage-activating factor from rainbow trout Salmo gairdneri leucocytes.
Rainbow trout head kidney and blood leucocytes are shown to be capable of secreting a soluble macrophage-activating factor (MAF) after stimulation with concanavalin A (Con A). The presence of phorbol myristate acetate (PMA) as a co-stimulant increased the production of MAF. Both respiratory burst activity (nitroblue tetrazolium, NBT, reduction and H2O2 production) and bactericidal activity were enhanced after incubation of resident or elicited macrophages with the MAF-containing supernatants for 48-72 hr. The target culture period before the addition of MAF did not affect their responsiveness, but a continuous presence of MAF was necessary for maximal stimulation.


Streptococcus pyogenes Phospholipase A2 Induces the Expression of Adhesion Molecules on Human Umbilical Vein Endothelial Cells and Aorta of Mice.
The Streptococcus pyogenes phospholipase A2 (SlaA) gene is highly conserved in the M3 serotype of group A S. pyogenes, which often involves hypervirulent clones. However, the role of SlaA in S. pyogenes pathogenesis is unclear. Herein, we report that SlaA induces the expression of intercellular adhesion molecule 1 (ICAM1) and vascular cell adhesion molecule 1 (VCAM1) via the arachidonic acid signaling cascade. Notably, recombinant SlaA induced ICAM1 and VCAM1 expression in human umbilical vein endothelial cells (HUVECs), resulting in enhanced adhesion of human monocytic leukemia (THP-1) cells. However, C134A, a variant enzyme with no enzymatic activity, did not induce such events. In addition, culture supernatants from S. pyogenes SSI-1 enhanced the adhesion of THP-1 cells to HUVECs, but culture supernatants from the ΔslaA isogenic mutant strain had limited effects. Aspirin, a cyclooxygenase 2 inhibitor, prevented the adhesion of THP-1 cells to HUVECs and did not induce ICAM1 and VCAM1 expression in HUVECs treated with SlaA. However, zileuton, a 5-lipoxygenase inhibitor, did not exhibit such effects. Furthermore, pre-administration of aspirin in mice intravenously injected with SlaA attenuated the transcriptional abundance of ICAM1 and VCAM1 in the aorta. These results suggested that SlaA from S. pyogenes stimulates the expression of adhesion molecules in vascular endothelial cells. Thus, SlaA contributes to the inflammation of vascular endothelial cells upon S. pyogenes infection.


[Sequential changes of vascular intimal ultrastructure in experimental cerebral vasospasm induced by oxyhemoglobin. Scanning electron microscopic study].
Organic changes of vessel wall may play an important role in the pathophysiology of vasospasm after subarachnoid hemorrhage. Sequential changes of intimal ultrastructure in experimental vasospasm induced oxyhemoglobin were investigated by scanning electron microscope. Thirty-four cats were used for this study. The basilar artery was exposed by transcervico-transclival approach. Oxyhemoglobin solution was applied under the arachnoid membrane around the artery in 16 cats at hourly intervals. Of 16 cats, 3 were sacrificed at 1 hour after the first application of the solution, 3 at 3 hours, 3 at 6 hours, 3 at 12 hours, 4 at 24 hours. Three sham-operated cats treated by artificial CSF were used as the control together with 5 untreated normal cats. All procedures were performed under aseptic condition. Perfusion fixation was done. The luminal surface and the cut surface made by freeze-fracture method were investigated by scanning electron microscope. As oxyhemoglobin solution, oxyhemoglobin-rich hemolysate was used and the concentration was 5.5 mM. By hourly application, continuous vasoconstriction of about 70% of the control diameter was obtained. In the control, the endothelial cell layer was flat. The elastic lamina had mild waving, and the luminal surface was smooth. In 1- and 3-hour groups, the elastic lamina was corrugated and the endothelial cells were protruded into the lumen in the depressed portion of corrugation. In 6- and 12-hour groups, degenerative changes of the endothelial cells, crater-formation and ballooning, were seen. Some blood-born cells adhered to the luminal surface in such cases. In 24-hour group, the changes of the endothelial cells became more remarkable.(ABSTRACT TRUNCATED AT 250 WORDS)


Altered fractionation schedules in radiation treatment: a review.
Conventionally fractionated radiotherapy is delivered in 1.8- to 2.0-Gy fractions. With increases in understanding of radiation and tumor biology, various alterations of radiotherapy schedules have been tested in clinical trials and are now regarded by some as standard treatment options. Hyperfractionation is delivered through a greater number of smaller treatment doses. Accelerated fractionation decreases the amount of time over which radiotherapy is delivered typically by increasing the number of treatments per day. Hypofractionation decreases the number of fractions delivered by increasing daily treatment doses. Furthermore, many of these schedules have been tested with concurrent chemotherapy regimens. In this review, we summarize the major clinical studies that have been conducted on altered fractionation in various disease sites.


A three-degree-of-freedom thin-film PZT-actuated microactuator with large out-of-plane displacement.
A novel three degree-of-freedom microactuator based on thin-film lead-zirconate-titanate (PZT) is described with its detailed structural model. Its central rectangular-shaped mirror platform, also referred to as the stage, is actuated by four symmetric PZT bending legs such that each leg provides vertical translation for one corner of the stage. It has been developed to support real-time in vivo vertical cross-sectional imaging with a dual axes confocal endomicroscope for early cancer detection, having large displacements in three axes (z, θx, θy) and a relatively high bandwidth in the z-axis direction. Prototype microactuators closely meet the performance requirements for this application; in the out-of-plane (z-axis) direction, it has shown more than 177 μm of displacement and about 84 Hz of structural natural frequency, when two diagonal legs are actuated at 14V. With all four legs, another prototype of the same design with lighter stage mass has achieved more than 430 μm of out-of-plane displacement at 15V and about 200 Hz of bandwidth. The former design has shown approximately 6.4° and 2.9° of stage tilting about the x-axis and y-axis, respectively, at 14V. This paper also presents a modeling technique that uses experimental data to account for the effects of fabrication uncertainties in residual stress and structural dimensions. The presented model predicts the static motion of the stage within an average absolute error of 14.6 μm, which approaches the desired imaging resolution, 5 μm, and also reasonably anticipates the structural dynamic behavior of the stage. The refined model will support development of a future trajectory tracking controller for the system.


Serology of Chlamydia trachomatis in infants.
Sera from 502 infants with pneumonia were tested for antibodies to Chlamydia trachomatis by the microimmunofluorescence test; 175 (34.9%) were positive for IgM antibodies (titer, greater than or equal to 1:32). Chlamydiae were recovered from 42 (46.2%) of 91 IgM antibody-positive infants as compared with six (3.3%) of 181 IgM antibody-negative infants (P less than 0.0001). Two (4%) of 46 of the infants with inclusion conjunctivitis, but not pneumonia, had titers of IgM antibody of greater than or equal to 1:32; both shed the organism from the rectum. IgM antibody to C. trachomatis is not maternally transmitted to infants and was detected at a low rate (1.1%) in infants with nonpneumonic conditions. Diagnosis of pneumonia due to Chlamydia in infants by isolation of the agent is slow and unreliable. High levels of IgM antibody (greater than 1:32) appear to reflect a systemic chlamydial infection and offer the possibility of a same-day diagnosis. Thus, the detection of specific IgM antibodies to C. trachomatis may be the method of choice in diagnosing chlamydial pneumonia in infants.


Rhizopogon spore bank communities within and among California pine forests.
In this study we examine the distribution of Rhizopogon species in spore banks from five California pine forests. Four of the forest sites were discontinuous populations of Pinus muricata and a fifth was a Pinus ponderosa stand in Sierra National Forest. Rhizopogon species were retrieved by bioassaying the soils with pine seedlings followed by isolation of axenic cultures from individual root tips with typical Rhizopogon ectomycorrhizal morphology. The cultures were screened by ITS-RFLP and all unique patterns were sequenced. These sequences then were compared with those derived from identified sporocarp material. Bioassaying proved to be an efficient way to bring Rhizopogon species into culture. Approximately 50% of the pots contained ectomycorrhizal tips with Rhizopogon-like morphology, and axenic Rhizopogon cultures were obtained from half these pots. Our results showed that Rhizopogon spores usually are well distributed within local forest areas, while there is significant structuring of species at the regional scale. Spore longevity and homogenization by soil and water movement might explain their distribution within local forest areas, while the regional pattern might be explained by limited long distance dispersal or climatic and edaphic differences.


The TEG®6s on Shaky Ground? A Novel Assessment of the TEG®6s Performance under a Challenging Condition.
Thromboelastography® (TEG®) is used to guide clinical decision-making across many medical and surgical subspecialties. Advances in this field have resulted in analyzers becoming increasingly user friendly, and have led to a reduction in the possibility of user error. The new TEG®6s does not come with the warnings of vibration and movement avoidance of its predecessor. It was decided to test the capability of this device while being subject to motion. TEG®6s machine 1 was placed in an environment free from motion. TEG®6s machine 2 was placed on a flatbed platelet agitator, which would expose the device to sudden and continual motion. Blood from the same healthy volunteer was pipetted into cartridges and inserted into both machines. Testing was commenced on machine 2 simultaneously with the agitator being activated. Visual and numerical data were collected. All measured parameters were significantly different (p < .05) between the motion and motion-free groups apart from CK R-Time, CRT R-Time, CRT Angle, and CRT Ly30. The TEG®6s results differ significantly when the analyzer is exposed to a set amount of motion. Such motion should be avoided if results are to be relied upon.


Morphological variation, phylogenetic relationships, and geographic distribution of the Baenidae (Testudines), based on new specimens from the Uinta Formation (Uinta Basin), Utah (USA).
We described newly discovered baenid specimens from the Uintan North American Land Mammal Age (NALMA), in the Uinta Formation, Uinta Basin, Utah. These specimens include a partial skull and several previously undescribed postcranial elements of Baena arenosa, and numerous well-preserved shells of B. arenosa and Chisternon undatum. Baenids from the Uintan NALMA (46.5-40 Ma) are critical in that they provide valuable insight into the morphology and evolution of the diverse and speciose baenid family near the end of its extensive radiation, just prior to the disappearance of this clade from the fossil record. These Uintan specimens greatly increase the known variation in these late-surviving taxa and indicate that several characters thought to define these species should be reassessed. The partial cranium of B. arenosa, including portions of the basicranium, neurocranium, face, and lower jaw, was recently recovered from Uinta B sediments. While its morphology is consistent with known specimens of B. arenosa, we observed several distinct differences: a crescent-shaped condylus occipitalis that is concave dorsally, tuberculum basioccipitale that flare out laterally, and a distinct frontal-nasal suture. The current sample of plastral and carapacial morphology considerably expands the documented variation in the hypodigms of B. arenosa and C. undatum. Novel shell characters observed include sigmoidal extragular-humeral sulci, and small, subtriangular gular scutes. Subadult specimens reveal ontogenetic processes in both taxa, and demonstrate that diagnostic morphological differences between them were present from an early developmental age.


Lost in digitization - A systematic review about the diagnostic test accuracy of digital pathology solutions.
Digital pathology solutions are increasingly implemented for primary diagnostics in departments of pathology around the world. This has sparked a growing engagement on validation studies to evaluate the diagnostic performance of whole slide imaging (WSI) regarding safety, reliability, and accuracy. The aim of this review was to evaluate the performance of digital pathology for diagnostic purposes compared to light microscopy (LM) in human pathology, based on validation studies designed to assess such technologies. In this systematic review based on PRISMA guidelines, we analyzed validation studies of WSI compared with LM. We included studies of diagnostic performance of WSI regarding diagnostic test accuracy (DTA) indicators, degree of overdiagnosis, diagnostic concordance, and observer variability as a secondary outcome. Overdiagnosis is (for example) detecting a pathological condition that will either not progress or progress very slowly. Thus, the patient will never get symptoms from this condition and the pathological condition will never be the cause of death. From a search comprising four databases: PubMed, EMBASE, Cochrane Library, and Web of Science, encompassing the period 2010-2021, we selected and screened 12 peer-reviewed articles that fulfilled our selection criteria. Risk of bias was conducted through QUADAS-2 tool, and data analysis and synthesis were performed in a qualitative format. We found that diagnostic performance of WSI was not inferior to LM for DTA indicators, concordance, and observer variability. The degree of overdiagnosis was not explicitly reported in any of the studies, while the term itself was used in one study and could be implicitly calculated in another. WSI had an overall high diagnostic accuracy based on traditional accuracy measurements; however, the degree of overdiagnosis is unknown.


Synthesis of 3-substituted thieno [2, 3-d] pyrimidin-4(3H)-one-2-mercaptoacetic acids and their ethyl esters for pharmacological screening.
3-Substituted thieno [2, 3-d] pyrimidin-4(3H)-one-2-mercaptoacetic acids and their ethyl esters were synthesized from 2-mercaptothieno [2, 3-d] pyrimidin-4(3H]-ones, which were obtained by cyclization of thienylthioureas in acidic medium. Analgesic, anti-inflammatory, and anticonvulsant activities were found in some of these compounds. Significant antimicrobial activity was exhibited by thienylthioureas.


[Cholesterol goal attainment with lipid lowering drugs. The COMETA Mexico Trial].
In a retrospective study to determine rate of patients attaining therapeutic LDL-C goal values with lipid-lowering drugs, 20 specialists and general practitioners were selected who enrolled 120 patients whose lipids were measured after at least 12 weeks of treatment. They were grouped in three categories: group A (absolute risk of CHD in 10 years <10%); group B, with 10-20% risk, and group C, with >20% risk. Goal LDL-C values were <160 mg/dL for group A, <130 for group B, and <100 for group C. Mean age was 57 +/- 12 years, 59% were males, and 51% were in group C; 83% took statins, 12% fibrates alone, and 5%, combinations. Atorvastatin and simvastatin were the most used drugs, at medium doses (mean 12 and 27 mg/day). LDL-C was reduced 25%; overall, 22% of patient doses were adjusted. Therapeutic goals were attained in 29% with initial doses and 42% at the end of study. Goal values were better attained in groups with lower risk. No differences were noticed among distinct physician categories. Data show poor compliance with international guidelines and insufficient attainment of therapeutic goals.


[Clinical and functional results after transfemoral thrombectomy for iliofemoral deep venous thrombosis: a 5-year-follow-up].
The optimal therapy of deep pelvic and leg venous thrombosis is still a matter of debate. The purpose of our study was to evaluate early and late results of iliofemoral thrombectomy with regard to the prevention of the development of a postthrombotic syndrome. Between 1996 and 2000, 57 patients underwent transfemoral venous thrombectomy for acute iliofemoral thrombosis. 30 patients were reexamined after a mean of 60.4 months. At follow-up, the patency of the venous segments as well as the development of reflux was investigated by duplex-ultrasound. Furthermore, clinical signs and symptoms of chronic venous insufficiency as well as the subjective satisfaction of the patients with the operation were recorded. Postoperatively the veins of the lower leg were completely recanalized in 25 % of the cases, those of the thigh in 52.3 %. The patency rate at the level of the groin, the pelvis and the caval vein were 92.5, 86 and 100 %, respectively. At follow-up, the veins of the lower limb, the thigh and the pelvis were patent in 76.7 % each and in 73.3 % at groin-level. The caval vein was completely recanalized in all cases. Reflux occurred in 12 patients. 26.7 % of the patients showed no signs of a postthrombotic syndrome. 63.3 % had mild changes including dilated superficial veins and swelling tendency, and only in 10 % trophic skin changes were apparent. A healed or active ulceration did not occur in any case. Except one, all patients were satisfied with the results of the thrombectomy. Transfemoral thrombectomy for acute iliofemoral venous thrombosis offers good early and late results in terms of preserving venous function and reducing symptoms of venous insufficiency. In our patient population, the development of a severe postthrombotic syndrome could be reduced effectively.


Glutathione peroxidase and glutathione reductase activities towards glutathione-derived antioxidants.
A new class of glutathione derivatives with antioxidant properties has been prepared by transformation of the NH2 group into a pyrrole ring with various substitutions at the 2 and 5 positions. Due to steric hindrance and/or hydrophobicity of the 2-5-disubstituted pyrrole ring, the reduced glutathione derivatives are poor substrates of the glutathione peroxidase and do not effectively compete with GSH. The oxidized glutathione derivatives are, in turn, relatively good substrates (Km = 1.5 mM) of the glutathione reductase as compared to natural oxidized glutathione (Km = 0.51 mM) but are not effective competitors of the enzyme. It can be considered that the new glutathione derivatives do not strongly interfere with the natural enzymatic defence against fatty acid hydroperoxides formed during an oxidative stress.


CVOT Summit 2022 Report: new cardiovascular, kidney, and glycemic outcomes.
The 8th Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Kidney, and Glycemic Outcomes was held virtually on November 10-12, 2022. Following the tradition of previous summits, this reference congress served as a platform for in-depth discussion and exchange on recently completed outcomes trials as well as key trials important to the cardiovascular (CV) field. This year's focus was on the results of the DELIVER, EMPA-KIDNEY and SURMOUNT-1 trials and their implications for the treatment of heart failure (HF) and chronic kidney disease (CKD) with sodium-glucose cotransporter-2 (SGLT2) inhibitors and obesity with glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists. A broad audience of primary care physicians, diabetologists, endocrinologists, cardiologists, and nephrologists participated online in discussions on new consensus recommendations and guideline updates on type 2 diabetes (T2D) and CKD management, overcoming clinical inertia, glycemic markers, continuous glucose monitoring (CGM), novel insulin preparations, combination therapy, and reclassification of T2D. The impact of cardiovascular outcomes on the design of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) trials, as well as the impact of real-world evidence (RWE) studies on the confirmation of CVOT outcomes and clinical trial design, were also intensively discussed. The 9th Cardiovascular Outcome Trial Summit will be held virtually on November 23-24, 2023 ( http://www.cvot.org ).


[Heparins: from conventional to current approaches in the management of acute coronary ischemic syndromes].
The use of heparins in acute coronary syndromes has been established as antithrombine indication. In acute myocardial infarction, it is considered an adjunct therapy to reperfusion strategies. In patients with angina, this antithrombine therapy experts a synergic effect with antiplatelet drugs, which also have an antithrombine effect. This pharmacological information movides the possibility to use the traditional unfractioned heparin (UFH) and low molecular heparin (LMH), both are antithrombine drugs. The advantage of these low molecular heparins is their biodisponibility and easier use. Both types of heparins are relevant since there is valid information establishing that LMH is useful in acute coronary syndromes. Such as acute myocardial infarction (AMI), yielding better results than the UFH. Newer drugs, the pentasaccharides, have been reported recently, which. Newer drugs are small fractions of heparin, with antithrombine effects and which seem to be more powerful and effective offering better results. These drugs have been named pentasaccharides.


Mevalonolactone disrupts mitochondrial functions and induces permeability transition pore opening in rat brain mitochondria: Implications for the pathogenesis of mevalonic aciduria.
Mevalonic aciduria (MVA) is caused by severe deficiency of mevalonic kinase activity leading to tissue accumulation and high urinary excretion of mevalonic acid (MA) and mevalonolactone (ML). Patients usually present severe neurologic symptoms whose pathophysiology is poorly known. Here, we tested the hypothesis that the major accumulating metabolites are toxic by investigating the in vitro effects of MA and ML on important mitochondrial functions in rat brain and liver mitochondria. ML, but not MA, markedly decreased mitochondrial membrane potential (ΔΨm), NAD(P)H content and the capacity to retain Ca2+ in the brain, besides inducing mitochondrial swelling. These biochemical alterations were totally prevented by the classical inhibitors of mitochondrial permeability transition (MPT) cyclosporine A and ADP, as well as by ruthenium red in Ca2+-loaded mitochondria, indicating the involvement of MPT and an important role for mitochondrial Ca2+ in these effects. ML also induced lipid peroxidation and markedly inhibited aconitase activity, an enzyme that is highly susceptible to free radical attack, in brain mitochondrial fractions, indicating that lipid and protein oxidative damage may underlie some of ML-induced deleterious effects including MTP induction. In contrast, ML and MA did not compromise oxidative phosphorylation in the brain and all mitochondrial functions evaluated in the liver, evidencing a selective toxicity of ML towards the central nervous system. Our present study provides for the first time evidence that ML impairs essential brain mitochondrial functions with the involvement of MPT pore opening. It is therefore presumed that disturbance of brain mitochondrial homeostasis possibly contributes to the neurologic symptoms in MVA.


Effect of intramuscular injection of hepatocyte growth factor plasmid DNA with electroporation on bleomycin-induced lung fibrosis in rats.
So far, there is no efficient treatment for pulmonary fibrosis. The objective of this study was to determine whether intramuscular injection of the hepatocyte growth factor (HGF) plasmid DNA by in vivo electroporation could prevent bleomycin-induced pulmonary fibrosis in rats, and to investigate the possible mechanisms. Twenty male Wistar rats were randomly divided into four groups: control group (group C), model group (group M), early intervention group (group I) and late intervention group (group II). Groups M, I and II were intratracheally infused with bleomycin, then injected the plasmid pcDNA3.1-hHGF to group I on day 7, 14 and 21. Group II received the same treatment like Group I on day 14 and 21. All the rats were killed on day 28 after bleomycin injection. We detected Homo HGF expression in the rats with ELISA method and estimated the pathological fibrosis score of lung tissue using hematoxylin eosin (HE) and Massion staining. The mRNA expression of transforming growth factor-beta1 (TGF-beta1), cycloxygenase-2 (COX-2), and rat HGF in rat pulmonary parenchyma were evaluated by RT-PCR. Immunohistochemistry and Western blotting were performed to determine the protein expression of transforming TGF-beta1 and COX-2 in lung parenchyma. The plasmid pcDNA3.1-hHGF could express hHGF in NIH3T3 cells and the hHGF protein is secreted into the culture medium. The expression of hHGF protein could be monitored in quadriceps muscle, plasma and lung in Groups I and II. Pulmonary fibrosis levels of Groups I and II were obviously lower than that of group M (P < 0.05). Expression of TGF-beta1 protein and mRNA in lung tissue was markedly decreased in Groups I and II compared with Group M (P < 0.05). The level of expression of HGF and COX-2 mRNA was higher in Groups I and II than in Group M (P < 0.05). Injection of the plasmid pcDNA3.1-hHGF into skeletal muscle with electroporation has a potential role in the treatment of bleomycin-induced lung fibrosis. Exogenous HGF may inhibit the expression of TGF-beta1 and regulate the crosstalk between AECs and mesenchymal fibroblasts.


Proton antenna effect of the gamma-cyclodextrin outer surface, measured by excited state proton transfer.
The reversible proton dissociation and geminate recombination of the common photoacid, 8-hydroxypyrene-1,3,6-trisulfonate (pyranine), either in dilute aqueous solution or when forming a complex with gamma-cyclodextrin (gamma-CD), has been studied by time-resolved fluorescence spectroscopy and supplemented by molecular modeling and dynamics simulations. We find that the dissociation rate of the proton from the excited molecule was decreased to about approximately 50% of its value in water, while the rate of recombination was doubled. These observations were evaluated by molecular modeling of the reactants at atomic resolution. The combination of the two methodologies indicates that the pyranine in the complex can assume more than one level of interaction with the solvent. The polysugar torus surrounding the pyranine perturbs the hydrogen bond in the dye's immediate vicinity and deforms the electrostatic potential inside the Coulomb cage, causing major deviations from a simple spheric symmetry. These observations can account for the special kinetic features measured for the complex. We suggest that this system can be used as a basic model for evaluating the mechanism of proton transfer in non-homogeneous systems, such as the surface of proteins or biomembranes.


Quantitative comparison of protein dynamics in live cells and in vitro by in-cell (19)F-NMR.
Here we describe how a (19)F-probe incorporated into an endogenous protein by a chemical biology method revealed protein dynamics. By explicit determination of ligand-bound and unbound structures with X-ray crystallography, the quantitative comparison of the protein's dynamics in live cells and in vitro is presented. These results clearly demonstrated the greater conformational fluctuations of the intracellular protein, partially due to macromolecular crowding effects.


Reducing Dietary Sodium to 1000 mg per Day Reduces Neurovascular Transduction Without Stimulating Sympathetic Outflow.
The American Heart Association recommends no more than 1500 mg of sodium/day as ideal. Some cohort studies suggest low-sodium intake is associated with increased cardiovascular mortality. Extremely low-sodium diets (≤500 mg/d) elicit activation of the renin-angiotensin-aldosterone system and stimulate sympathetic outflow. The effects of an American Heart Association-recommended diet on sympathetic regulation of the vasculature are unclear. Therefore, we assessed whether a 1000 mg/d diet alters sympathetic outflow and sympathetic vascular transduction compared with the more commonly recommended 2300 mg/d. We hypothesized that sodium reduction from 2300 to 1000 mg/d would not affect resting sympathetic outflow but would reduce sympathetic transduction in healthy young adults. Seventeen participants (age: 26±2 years, 9F/8M) completed 10-day 2300 and 1000 mg/d sodium diets in this randomized controlled feeding study (crossover). We measured resting renin activity, angiotensin II, aldosterone, blood pressure, muscle sympathetic nerve activity, and norepinephrine. We quantified beat-by-beat changes in mean arterial pressure and leg vascular conductance (femoral artery ultrasound) following spontaneous sympathetic bursts to assess sympathetic vascular transduction. Reducing sodium to 1000 mg/d increased renin activity, angiotensin II, and aldosterone ( P<0.01 for all) but did not alter mean arterial pressure (78±2 versus 77±2 mm Hg, P=0.56), muscle sympathetic nerve activity (13.9±1.3 versus 13.9±0.8 bursts/min, P=0.98), or plasma/urine norepinephrine. Sympathetic vascular transduction decreased ( P<0.01). These data suggest that reducing sodium from 2300 to 1000 mg/d stimulates the renin-angiotensin-aldosterone system, does not increase resting basal sympathetic outflow, and reduces sympathetic vascular transduction in normotensive adults.


[Prionic neuroinvasion and cerebellar lesion in Creutzfeldt-Jakob disease].
Examining the histological brain sections of patients with Creutzfeldt-Jakob disease (CJD) showed the accumulation of PrP(CJD) in the cerebellar cortical layers. In nCJD, the prion accumulated mainly in the granular layer in the area of synapses of moss fibers with granular cell dendrites in the cerebellar glomeruli and in the molecular layer in the area of the synapses formed by granular cell axons and great stellate neurons of the granular layer with the dendrites of Purkinje's piriform cells of busket cells and Golgi's cells. PrP(CJD) amyloid plaques were formed in these regions. In sporadic CJD, PrP(CJD) accumulated only in the cerebellar molecular layer in the area of the synapses formed by climbing fibers with the dendrites of Purkinje cells. The findings lead to the conclusion that prion spreads along different nerve fibers through the synapses. The preserved Purkinje cells contacting the plaques suggest that prion is not itself highly neurotoxic.


An integrated assessment of histopathological changes of the enteric neuromuscular compartment in experimental colitis.
Bowel inflammatory fibrosis has been largely investigated, but an integrated assessment of remodelling in inflamed colon is lacking. This study evaluated tissue and cellular changes occurring in colonic wall upon induction of colitis, with a focus on neuromuscular compartment. Colitis was elicited in rats by 2,4-dinitrobenzenesulfonic acid (DNBS). After 6 and 21 days, the following parameters were assessed on paraffin sections from colonic samples: tissue injury and inflammatory infiltration by histology; collagen and elastic fibres by histochemistry; HuC/D, glial fibrillar acidic protein (GFAP), proliferating cell nuclear antigen (PCNA), nestin, substance P (SP), von Willebrand factor, c-Kit and transmembrane 16A/Anoctamin1 (TMEM16A/ANO1) by immunohistochemistry. TMEM16A/ANO1 was also examined in isolated colonic smooth muscle cells (ICSMCs). On day 6, inflammatory alterations and fibrosis were present in DNBS-treated rats; colonic wall thickening and fibrotic remodelling were evident on day 21. Colitis was associated with both an increase in collagen fibres and a decrease in elastic fibres. Moreover, the neuromuscular compartment of inflamed colon displayed a significant decrease in neuron density and increase in GFAP/PCNA-positive glia of myenteric ganglia, enhanced expression of neural SP, blood vessel remodelling, reduced c-Kit- and TMEM16A/ANO1-positive interstitial cells of Cajal (ICCs), as well as an increase in TMEM16A/ANO1 expression in muscle tissues and ICSMCs. The present findings provide an integrated view of the inflammatory and fibrotic processes occurring in the colonic neuromuscular compartment of rats with DNBS-induced colitis. These morphological alterations may represent a suitable basis for understanding early pathophysiological events related to bowel inflammatory fibrosis.


Differential expression of two prolactin and growth hormone genes during early development of tilapia (Oreochromis mossambicus) in fresh water and seawater: implications for possible involvement in osmoregulation during early life stages.
The possible involvement of prolactin (PRL) and growth hormone (GH) in osmoregulation during early life stages of the tilapia (Oreochromis mossambicus) was examined by in situ hybridization and immunocytochemistry using synthetic oligonucleotide probes and homologous antisera to two tilapia PRLs (PRL188 and PRL177) and GH. Hybridization signals for PRL188 mRNA were detected for the first time in newly hatched larvae (5 days after fertilization), and were significantly greater in larvae in fresh water (FW) than those in seawater (SW) until 10 days after hatching. PRL177 mRNA was detected in the pituitary of embryos 1 day before hatching. Although PRL177 gene expression in the embryo and newly hatched larvae in FW was not significantly different from those in SW, the expression was significantly greater in FW than in SW from Day 2 until Day 10. Hybridization signals for GH mRNA were first detected in newly hatched larvae. No significant differences in GH mRNA expression were observed between larvae in FW and those in SW. A stronger immunoreaction, a significantly larger PRL cell size, and a pituitary area containing PRL cells were observed in larvae hatched and maintained in FW, in those transferred from SW to FW, compared to larvae hatched and maintained in SW, and in those transferred from FW to SW. No significant difference was observed in the activity of GH cells between larvae in FW and those in SW. These results suggest that both PRLs are involved importantly in FW adaptation, whereas GH does not seem to play a critical role in osmoregulation during early stages of tilapia.


What to synthesize? From Emil Fischer to peptidomics.
The driving forces, incentives and strategic targets of peptide synthesis have undergone considerable evolution during the centenary following the pioneer work of Emil Fischer. In those days peptide synthesis was considered as a way of confirming the polypeptide theory of protein structure. The scientific community also expected (naively) that the synthesis would eventually lead to the creation of artificial living organisms. Only in the 1950s, when the first exact amino acid sequences were established did peptide chemistry obtain firmer ground and clearly defined targets. The total synthesis of peptide hormones and antibiotics became possible, providing valuable material for elucidating structure-functional relationships and the mechanisms of biological action. In the following years the number of peptides isolated from various biological sources grew with impressive speed and peptides became known as the most abundant, ubiquitous group of low molecular bioregulators. The design and synthesis of novel peptide based pharmaceuticals became an important area of peptide chemistry. At present we are facing the challenge of analysing the structures and bioactivities of total sets of peptides, i.e. peptidoms, present in concrete tissues or groups of cells. The results obtained along these lines at the IBCH RAS Institute of Bioorganic Chemistry are briefly considered in the review.


Investigation into the Effect of Atmospheric Particulate Matter (PM2.5 and PM10) Concentrations on GPS Signals.
The Global Positioning System (GPS) has been widely used in navigation, surveying, geophysical and geodynamic studies, machine guidance, etc. High-precision GPS applications such as geodetic surveying need millimeter and centimeter level accuracy. Since GPS signals are affected by atmospheric effects, methods of correcting or eliminating ionospheric and tropospheric bias are needed in GPS data processing. Relative positioning can be used to mitigate the atmospheric effect, but its efficiency depends on the baseline lengths. Air pollution is a serious problem globally, especially in developing countries that causes health problems to humans and damage to the ecosystem. Respirable suspended particles are coarse particles with a diameter of 10 micrometers or less, also known as PM10. Moreover, fine particles with a diameter of 2.5 micrometers or less are known as PM2.5. GPS signals travel through the atmosphere before arriving at receivers on the Earth's surface, and the research question posed in this paper is: are GPS signals affected by the increased concentration of the PM2.5/PM10 particles? There is no standard model of the effect of PM2.5/PM10 particles on GPS signals in GPS data processing, although an approximate generic model of non-gaseous atmospheric constituents (<1 mm) can be found in the literature. This paper investigates the effect of the concentration of PM2.5/PM10 particles on GPS signals and validates the aforementioned approximate model with a carrier-to-noise ratio (CNR)-based empirical method. Both the approximate model and the empirical results show that the atmospheric PM2.5/PM10 particles and their concentrations have a negligible effect on GPS signals and the effect is comparable with the noise level of GPS measurements.


A review of the application of deep learning in medical image classification and segmentation.
Big medical data mainly include electronic health record data, medical image data, gene information data, etc. Among them, medical image data account for the vast majority of medical data at this stage. How to apply big medical data to clinical practice? This is an issue of great concern to medical and computer researchers, and intelligent imaging and deep learning provide a good answer. This review introduces the application of intelligent imaging and deep learning in the field of big data analysis and early diagnosis of diseases, combining the latest research progress of big data analysis of medical images and the work of our team in the field of big data analysis of medical imagec, especially the classification and segmentation of medical images.


Retention of visa-trainee post-graduate residents in Canada: a retrospective cohort study.
Visa trainees (international medical graduates [IMG] who train in Canada under a student or employment visa) are expected to return home after completing their training. We examine the retention patterns of visa trainee residents funded by Canadian (regular ministry and other), foreign, or mixed sources. We linked data from the Canadian Post-MD Medical Education Registry with Scott's Medical Database for a retrospective cohort study. Eligible trainees were IMG visa trainees as of their first year of training, started their residency program no earlier than 2000, and exited training between 2006 and 2016. We used Cox regression to compare the retention of visa trainees by funding source. Of 1,913 visa trainees, 431(22.5%), 1353 (70.7%) and 129 (6.8%) had Canadian, foreign, or mixed funding, respectively. The proportion of trainees remaining in Canada decreased over time, with 35.5% (679/1913); 17.7% (186/1052); 10.8% (11/102) in Canada one, five, and ten years, respectively after their exit from PGME training. Trainees who remained on visas (HR: 1.91; [95% CI 1.59, 2.30]), were funded exclusively by foreign sources (HR: 1.46; [95% CI 1.25, 1.69]), and who had graduated from 'Western' countries (HR: 1.39; [95% CI 1.06, 1.84]) were more likely to leave Canada compared to trainees who became citizens/permanent residents, were funded by Canadian sources, or were visa graduates of Canadian medical schools, respectively. Most visa trainees leave Canada following their training. Trainees with Canadian connections (funding and/or change in legal status) were more likely to remain in Canada.


Persistent postmastectomy pain and pain-related physical and emotional functioning with and without a continuous paravertebral nerve block: a prospective 1-year follow-up assessment of a randomized, triple-masked, placebo-controlled study.
In a previous randomized, triple-masked, placebo-controlled study, the authors demonstrated that extending a single-injection paravertebral nerve block with a multiple-day perineural local anesthetic infusion improves analgesia and decreases pain-related dysfunction during the 3-day infusion but not subsequent to catheter removal within 1 month after mastectomy. This report describes a prospective follow-up study of the previously published trial to investigate the possibility that extending a single-injection paravertebral block with a multiple-day infusion may decrease persistent postsurgical pain as well as pain-induced emotional and functional dysfunction 1 year after mastectomy. Subjects undergoing uni- or bilateral mastectomy received unilateral (n = 24) or bilateral (n = 36) single-injection thoracic paravertebral block(s) with ropivacaine and perineural catheter(s). The subjects were randomized to receive either ropivacaine 0.4 % (n = 30) or normal saline (n = 30) via their catheters until the catheters were removed on postoperative day 3. Chronic pain and pain-related physical and emotional dysfunction were measured using the Brief Pain Inventory (BPI). No statistically significant difference between treatments 3 months after surgery was observed with the BPI. In contrast, after 12 months, only 4 subjects (13 %) who had received a perineural ropivacaine infusion reported pain-induced dysfunction compared with 14 (47 %) who had received saline infusion (P = 0.011). At 12 months, the mean BPI was 1.6 ± 4.6 for the subjects who received ropivacaine versus 5.9 ± 11.3 for the subjects who received saline (P = 0.007). Adding a multiple-day, continuous ropivacaine infusion to a single-injection ropivacaine paravertebral nerve block may result in a lower incidence of pain as well as pain-related physical and emotional dysfunction 1 year after mastectomy.


Core-Shell Nanoparticle Coating as an Interfacial Layer for Dendrite-Free Lithium Metal Anodes.
Lithium metal based batteries represent a major challenge and opportunity in enabling a variety of devices requiring high-energy-density storage. However, dendritic lithium growth has limited the practical application of lithium metal anodes. Here we report a nanoporous, flexible and electrochemically stable coating of silica@poly(methyl methacrylate) (SiO2@PMMA) core-shell nanospheres as an interfacial layer on lithium metal anode. This interfacial layer is capable of inhibiting Li dendrite growth while sustaining ionic flux through it, which is attributed to the nanoscaled pores formed among the nanospheres. Enhanced Coulombic efficiencies during lithium charge/discharge cycles have been achieved at various current densities and areal capacities.


Identification of patients who may benefit from prophylactic immunotherapy after bone marrow transplantation for acute myeloid leukemia on the basis of lymphocyte recovery early after transplantation.
Two hundred and one patients (median age, 29 years) with acute myeloid leukemia (AML) underwent bone marrow transplantation (BMT) from HLA-identical sibling donors after conditioning with melphalan-total-body irradiation (TBI) (57%), cyclophosphamide-TBI (35%), or chemotherapy alone (8%). Graft-versus-host disease (GVHD) prophylaxis included cyclosporine alone (68%), cyclosporine-methotrexate (26%), or T-cell depletion (6%). The probability of relapse was calculated as a function of the absolute lymphocyte count (10(9)/L) on days 27 to 30 posttransplant (<0.1 v >/=0.1, <0.2 v >/=0.2, and <0.3 v >/=0.3). In each of these 12 comparisons, the probability of relapse was higher for the group with the lower lymphocyte count. Because the difference was most significant (P = .004) for an absolute lymphocyte count of <0.2 on day 29 (3-year relapse probability, 42%) versus >/= 0.2 (16%), this variable was included in a Cox model to determine factors independently affecting relapse. Multivariate analysis showed that conditioning regimens other than melphalan-TBI, a low lymphocyte count on day 29, French-American-British (FAB) subtypes M4-7, and a nucleated cell dose of > 2.42 x 10(8)/kg was associated with a higher risk of relapse. We conclude that slow lymphocyte recovery after allogeneic BMT, to < 0.2 x 10(9)/L 29 days in this analysis, appears to be associated with a higher risk of relapse in patients with AML. This group of patients may benefit from posttransplant immune manipulations such as abbreviated GVHD prophylaxis, or donor cell or cytokine administration to enhance graft-versus-leukemia reactions to reduce relapse.


Residential context, walking and obesity: two African-American neighborhoods compared.
We compare walking and obesity rates in two African-American neighborhoods that are similar in urban form but different in level of neighborhood disadvantage. We find higher rates of utilitarian walking in the neighborhood with higher density and disadvantage and more destinations within walking distance. However levels of leisure walking and physical activity were not higher, and rates of obesity were not lower in the non-poor neighborhood with better maintenance, more sidewalks and recreational facilities. Different types of barriers to physical activity reported in the two neighborhoods and the high rates of overweight and obesity in both may explain the findings.


Is standing balance altered in individuals with chronic low back pain? A systematic review.
To examine the static standing balance of individuals with chronic low back pain when compared to a healthy control group. A search of available literature was done using PubMed, SPORTDiscus, CINAHL, and Scopus databases. Studies were included if they contained the following: (1) individuals with chronic low back pain 3 months or longer; (2) healthy control group; (3) quantified pain measurement; and (4) center of pressure measurement using a force plate. Two authors independently reviewed articles for inclusion, and assessed for quality using the Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross Sectional Studies. Cohen's d effect size was calculated to demonstrate the magnitude of differences between groups. Nine articles were included in this review. Quality scores ranged from 5/8 to 8/8. Although center of pressure measures were nonhomogeneous, subjects with chronic low back pain had poorer performance overall compared to healthy controls. Despite inconsistencies in statistical significance, effect sizes were frequently large, indicating a lack of sufficient power in the included studies. Data were insufficiently reported among certain studies, limiting the ability of direct study comparison. Results suggest that balance is impaired in individuals with chronic low back pain when compared to healthy individuals. Implications for rehabilitation Static balance is affected in individuals with chronic low back pain. Balance assessments should be completed for individuals with chronic low back pain. Results from balance assessments should be used to indicate areas of improvement and help guide the course of treatment, as well as reassess as treatment progresses.


Coating of magnetite with mercapto modified rice hull ash silica in a one-pot process.
In this research, mercapto-silica coated magnetite (Fe3O4-SiO2-SH) has been prepared in aqueous solution through a simple approach so called a one-pot process. The Fe3O4-SiO2-SH was prepared in nitrogen condition by mixing magnetite, 3-mercaptopropyltrimethoxysilane (MPTMS), and sodium silicate (Na2SiO3) solution extracted from rice hull ash, and adjusting the pH of 7.0 using hydrochloric acid. The residue was washed with deionized water, dried at 150°C and separated with an external magnetic field. In that work, the volume of MPTMS and Na2SiO3 was varied and the total amount of Si represented as silica was kept constant. Characters of the material including the functional group presence, the structure, the porosity, the morphology and stability toward various solvents were identified and evaluated. Results of characterization indicated that mercapto-silica has been coated magnetite particle with a simple one-pot process. Coating mercapto-silica on magnetite increases particle size, surface area, and chemical stability. Additionally, Fe3O4-SiO2-SH also shows high stability toward various organic solvents. The magnetic property of magnetite does not change after coating and the addition of nonmagnetic material still gives high value of maximum saturation magnetization. The presence of mercapto groups effective for interaction with heavy metal ions, the high chemical stability without removing the magnetic property promises the prospective application of Fe3O4-SiO2-SH in the future such as for separation and removal of heavy metal ions from aquatic environments.


Fat distribution, physical activity, and cardiovascular risk factors.
The purpose of this study was to report the relationship between fat distribution, physical activity (PA), and cardiovascular disease (CVD) risk factors. Percent fat, computed tomography intra-abdominal adipose tissue (IAF), anthropometrics, Baecke activity questionnaire, and CVD risk (blood pressure, cholesterol, HDL, HDL2, HDL3, IDL, LDL, VLDL, and triglycerides) were evaluated in 137 men 30-71 yr old. IAF was consistently more highly related to CVD risk than other fat distribution variables including percent fat and waist:hip ratio (r = 0.3-0.45). IAF was significantly related to CVD risk after adjusting for other fat distribution variables. With the exception of the sum of biceps, triceps, thigh, and calf skinfolds (peripheral skinfolds), which was negatively related to CVD risk, no other fat distribution variable had consistent significant partial correlations with CVD risk. PA was related to IAF after adjusting for peripheral skinfolds, but PA was not related to peripheral skinfolds after adjusting for IAF, indicating more active men have relatively low IAF. IAF was related to CVD risk after adjusting for PA, but PA was not related to CVD risk after adjusting for IAF. These results indicate that IAF is directly related to CVD risk while the lower CVD risk found with more active men is more directly related to the low IAF found in more active men.


Classification of suicidal behavior: a review and step toward integration.
The many forms of suicidal phenomena, including contemplated, attempted, and completed suicide, present significant problems to both researchers and practitioners. Although many attempts have been made to develop categories, agreement among the proposed systems has been more the exception than the rule. This article reviews theoretical and empirical efforts to define types of suicidal individuals and attempts to integrate them by means of higher-order categories of variables. These categories or "dimensions" are as follows: (1) descriptive, (2) situational, (3) psychological/behavioral, and (4) teleological. Implications for research and practice are discussed.


Haematopoietic colony stimulating factors CSF-1 and GM-CSF increase phosphatidylinositol 3-kinase activity in murine bone marrow-derived macrophages.
The activity of phosphatidylinositol (PI) 3-kinase was examined in murine bone marrow-derived macrophages (BMM) stimulated with the haematopoietic growth factors colony stimulating factor-1 (CSF-1) and granulocyte/macrophage-CSF (GM-CSF). PI 3-kinase was immunoprecipitated from cell lysates using anti-phosphotyrosine antibody or an antibody directed against the 85K subunit of PI 3-kinase, and the activity assayed by the phosphorylation of PI in the presence of [gamma 32P]-ATP. The results demonstrate that CSF-1 increases the activity of PI 3-kinase, as compared to the non-stimulated control, in murine macrophages. Maximum activity was seen after 10 min of stimulation with CSF-1 at 3000-5000 U/ml. The dose-response of CSF-1 is consistent with other biochemical effects of CSF-1 seen in the BMM. GM-CSF also stimulated PI 3-kinase activity although to a lesser extent than CSF-1, correlating well with their degree of mitogenic activity on the BMM. Non-mitogenic macrophage activating agents, such as the phorbol myristate acetate, lipopolysaccharide, concanavalin A and formyl-methionyl-leucyl-phenylalanine, did not significantly increase the PI 3-kinase activity. Furthermore, CSF-1 failed to stimulate PI 3-kinase activity in resident peritoneal macrophages, a population of macrophages with poor proliferative capacity. These results suggest that the PI 3-kinase activity may be involved in the haemopoietic growth factor signalling pathways regulating macrophage growth.


Single Carrier with Frequency Domain Equalization for Synthetic Aperture Underwater Acoustic Communications.
Phase-coherent underwater acoustic (UWA) communication systems typically employ multiple hydrophones in the receiver to achieve spatial diversity gain. However, small underwater platforms can only carry a single transducer which can not provide spatial diversity gain. In this paper, we propose single-carrier with frequency domain equalization (SC-FDE) for phase-coherent synthetic aperture acoustic communications in which a virtual array is generated by the relative motion between the transmitter and the receiver. This paper presents synthetic aperture acoustic communication results using SC-FDE through data collected during a lake experiment in January 2016. The performance of two receiver algorithms is analyzed and compared, including the frequency domain equalizer (FDE) and the hybrid time frequency domain equalizer (HTFDE). The distances between the transmitter and the receiver in the experiment were about 5 km. The bit error rate (BER) and output signal-to-noise ratio (SNR) performances with different receiver elements and transmission numbers were presented. After combining multiple transmissions, error-free reception using a convolution code with a data rate of 8 kbps was demonstrated.


Spin reorientation in the square-lattice antiferromagnets RMnAsO (R = Ce, Nd): density functional analysis of the spin-exchange interactions between the rare-earth and transition-metal ions.
The spin reorientation (SR) phenomenon of the square-lattice antiferromagnets RMnAsO (R = Ce, Nd) was investigated by analyzing the spin-exchange interactions between the rare-earth and the transition-metal ions (R(3+) and Mn(2+), respectively) on the basis of density functional calculations. It is found that the symmetry and strength of the Dzyaloshinskii-Moriya (DM) interaction are determined primarily by the partially filled 4f states of the R(3+) ions and that the DM and biquadratic (BQ) exchanges between the R(3+) and the Mn(2+) ions are unusually strong and control the observed spin reorientation phenomenon. Below their SR temperature, the Mn(2+) and Ce(3+) moments are orthogonal in CeMnAsO but are collinear in NdMnAsO, because the DM interaction dominates over the BQ interaction for CeMnAsO, while the opposite is the case for NdMnAsO. Experiments designed to test the implications of our findings are proposed.


Lack of activity of oral etoposide for relapsed intraocular retinoblastoma.
Intravenous etoposide is widely used in multiagent chemotherapy regimens for intraocular retinoblastoma despite the lack of phase II data documenting its efficacy. Because oral etoposide has been found to be highly effective in patients with relapsed medulloblastoma and neuroblastoma who had previously received intravenous etoposide, we investigated its use for intraocular retinoblastoma. A pilot trial of oral etoposide (50 mg/m2/ day for 21 days) in five children (6 eyes) with relapsed refractory intraocular retinoblastoma was performed. All had previously received chemotherapy, including intravenous etoposide in four patients, and all had received radiation therapy. Three patients (3 eyes) had vitreous seeds. Response was evaluated after one cycle. No serious acute toxicity was encountered, and no responses were noted. Four patients (5 eyes) had progressive disease. Stable disease was noted in one eye without vitreous disease. One patient developed secondary acute myeloid leukemia 30 months after exposure to oral etoposide. Oral etoposide was not an effective agent in this population. The role of etoposide in the treatment of higher risk intraocular retinoblastoma deserves further study.


What have we been looking at? A call for consistency in studies of primate vigilance.
Vigilance functions to detect threats. In primates, these threats emerge from both predators and conspecifics, but a host of other social, demographic, and ecological factors have been shown to influence primate vigilance patterns. The primate vigilance literature is thus characterized by considerable variation in findings, with inconsistent or contradictory results reported not only across different species but also within species and populations across studies. Some of this variation could emerge from fundamental differences in the methods employed, making comparisons across species and groups challenging. Furthermore, identifying consistent behavioral markers for the state of vigilance appears to have proved challenging in primates, leading to a range of definitions being developed. Deviation at this level leads directly into concomitant variation at the level of sampling methodologies. As a result, the primate vigilance literature currently presents a diverse series of approaches to exploring subtly different behaviors and phenomena. This review calls for a greater consistency in studying vigilance, with the aim of encouraging future research to follow similar principles leading to more comparable results. Identifying whether an animal is in a vigilant state is challenging for most field researchers; identifying and recording a more general behavior of "looking" should though be more achievable. Experimental approaches could then be employed to understand the compatibility "looking" has with predator detection (and other threats) in individual study systems. The outcome of this approach will allow researchers to understand the key determinants of looking in their study groups and explore threat detection probabilities given an individual or group's relative level of looking.


Actions of potassium channel openers in rat detrusor urinae.
This study was performed to investigate the action of potassium channel openers on the mechanical activity of detrusor muscle isolated from rats. Detrusor muscle strips, 15 mm in length, were myographied isometrically in an isolated organ bath. P 1060, RP 49356 and BRL 38277, potassium channel activators, reduced the basal tone and diminished the phasic activity of detrusor concentration-dependently. P 1060, RP 49356 and BRL 38227 suppressed the maximal responses to bethanechol and shifted the concentration-response curves of bethanechol-induced contraction to the right. RP 49356 and BRL 38227 reduced the contraction by low (20 mM) concentration of potassium. P 1060, however, diminished the high (80 mM) and low (20 mM) concentration of potassium-induced contraction. Glibenclamide, an inhibitor of ATP-dependent potassium channel, antagonized the suppressive action of P 1060, RP 49356 and BRL 38227 on the basal tone. Apamin or procaine did not antagonize it significantly. Based on these results, it is suggested that the relaxation of detrusor muscle strip caused by P 1060, RP 49356 and BRL 38227 may predominantly involve opening of the same potassium channel, i.e., the ATP-dependent potassium channel.


Muscle mechanical advantage of human walking and running: implications for energy cost.
Muscular forces generated during locomotion depend on an animal's speed, gait, and size and underlie the energy demand to power locomotion. Changes in limb posture affect muscle forces by altering the mechanical advantage of the ground reaction force (R) and therefore the effective mechanical advantage (EMA = r/R, where r is the muscle mechanical advantage) for muscle force production. We used inverse dynamics based on force plate and kinematic recordings of humans as they walked and ran at steady speeds to examine how changes in muscle EMA affect muscle force-generating requirements at these gaits. We found a 68% decrease in knee extensor EMA when humans changed gait from a walk to a run compared with an 18% increase in hip extensor EMA and a 23% increase in ankle extensor EMA. Whereas the knee joint was extended (154-176 degrees) during much of the support phase of walking, its flexed position (134-164 degrees) during running resulted in a 5.2-fold increase in quadriceps impulse (time-integrated force during stance) needed to support body weight on the ground. This increase was associated with a 4.9-fold increase in the ground reaction force moment about the knee. In contrast, extensor impulse decreased 37% (P < 0.05) at the hip and did not change at the ankle when subjects switched from a walk to a run. We conclude that the decrease in limb mechanical advantage (mean limb extensor EMA) and increase in knee extensor impulse during running likely contribute to the higher metabolic cost of transport in running than in walking. The low mechanical advantage in running humans may also explain previous observations of a greater metabolic cost of transport for running humans compared with trotting and galloping quadrupeds of similar size.


Rapid GLC determination of propranolol in human plasma samples.
A rapid GLC method for measuring plasma propranolol levels is reported. 4-Methylpropranolol was utilized as an internal standard. Pentafluoropropionate derivatives of propranolol and the internal standard eluted rapidly and gave good sensitivity under the conditions employed. The advantage of this procedure over previously reported methods is the speed of analysis, which is facilitated by rapid elution of contaminant peaks.


Phase engineering of seamless heterophase homojunctions with co-existing 3R and 2H phases in WS2 monolayers.
Self-organized semiconductor-semiconductor heterostructures (3R-2H) that coexist in atomically thin 2D monolayers forming homojunctions are of great importance for next-generation nanoelectronics and optoelectronics applications. Herein, we investigated the defect controlled growth of heterogeneous electronic structure within a single domain of monolayer WS2 to enable in-plane homojunctions consisting of alternate 2H semiconducting and 3R semiconducting phases of WS2. X-ray photoelectron, Raman, and photoluminescence spectroscopy along with fluorescence and Kelvin probe force microscopy imaging confirm the formation of homojunctions, enabling a direct correlation between chemical heterogeneity and electronic heterostructure in the atomically thin WS2 monolayer. Quantitative analysis of phase fractions shows 59% stable 2H phase and 41% metastable 3R phase estimated over WS2 flakes of different sizes. Time-resolved fluorescence lifetime imaging confirms distinct contrast between 2H and 3R phases with two distinct lifetimes of 3.2 ns and 1.1 ns, respectively. Kelvin probe force microscopy imaging revealed an abrupt change in the contact potential difference with a depletion width of ∼2.5 μm, capturing a difference in work function of ∼40 meV across the homojunction. Further, the thermal stability of coexisting phases and their temperature dependent optical behavior show a distinct difference among 2H and 3R phases. The investigated aspects of the controlled in plane growth of coexisting phases with seamless homojunctions, their properties, and their thermal stability will enable the development of nanoscale devices that are free from issues of lattice mismatch and grain boundaries.


An outbreak of norovirus linked to oysters in Tasmania.
Norovirus is the most commonly reported virus in shellfish related gastroenteritis outbreaks. In March 2013 an investigation was conducted following the receipt of reports of gastroenteritis after the consumption of oysters at private functions in Tasmania. Cases were ascertained through general practitioners, emergency departments, media releases and self-reporting. Of the 306 cases identified in Tasmania, ten faecal specimens were collected for laboratory testing and eight were positive for norovirus (GII.g). The most common symptoms were vomiting (87%), diarrhoea (85%), myalgia (82%) and fever (56%). The implicated oysters were traced to a single lease from which they were harvested and distributed locally and interstate. Nationally 525 cases were identified from Tasmania (306), Victoria (209), New South Wales (8) and Queensland (2). This report highlights the consequences of norovirus outbreaks in shellfish, even with rapid identification, trace back and removal of the implicated product from the market.